Designing of Stable Co-crystals of Zoledronic Acid Using Suitable Coformers

Abstract

In this present study a new co-crystals of zoledronic acid with DL-tartaric acid and nicotinamide has been developed with improved solubility. Zoledronic acid is a class III drug with poor oral bioavailability due to its poor permeability and low aqueous solubility; hence an attempt has been made to improve its solubility by co-crystallization technology. Pharmaceutical cocrystals are multi-component crystals with a stoichiometric ratio of active pharmaceutical ingredients (APIs) and cocrystal coformers (CCFs) that are assembled by noncovalent interactions such as hydrogen bonds, π-π packing, and Vander Waals forces. In this study the coformers selected were DL-tartaric acid and nicotinamide based on ease of hydrogen bond formation. The co-crystal of zoledronic acid with DL-tartaric acid were prepared in three ratios (1 : 1, 1 : 2 and 2 : 1) by slow solvent evaporation method and with nicotinamide in 1 : 1 ratio by dry grinding method. The formation of co-crystal was confirmed by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and Fourier transform (FT)IR. The dynamic solubility of co-crystals with DL-tartaric acid in the ratios 1 : 1, 1 : 2 and 2 : 1 increased by fold as compared to pure drug.

High affinity zoledronate-based metal complex nanocrystals to potentially treat osteolytic metastases

“…14,16,17 It has been established that most of the drug undergoes renal clearance due to its significantly low bioavailability (o1%) and gastrointestinal permeation. [18][19][20] These attributes result in a maximum plasma concentration of 1 mM for the drug, which represents a 10-100x lower concentration than that needed to kill cancer cells in vitro. 21 However, recent studies have demonstrated that ZOLE exhibits direct cytotoxicity effects against human cancer cell models, recommending its use as a chemotherapeutic agent.…”

Pembentukan Dan Karakterisasi Fisika Kimia Ko-Kristal Piroxicam-Asam Tartrat-Sakarin Dengan Metode Solvent Drop Grinding

“…Koformer yang digunakan dalam penelitian ini adalah asam tartrat dan sakarin. Asam tartrat memiliki gugus fungsi asam karboksilat, sedangkan sakarin memiliki gugus fungsi amida, sehingga diharapkan dapat berikatan dengan gugus fungsi amida dari piroxicam [9], [10]. Metode yang digunakan dalam penelitian ini adalah metode solvent drop grinding (SDG).…”

Novel Pharmaceutical Cocrystals and Solvate Crystals of Nobiletin, a Citrus Flavonoid with Potent Pharmacological Activity

“…22) Moreover, there have been reports on improvements in the solubility, hygroscopicity and physical stability of the compounds. [23][24][25][26][27] Examples of drugs using the co-crystallization method include the sodium-glucose transporter 2 (SGLT2) inhibitors for diabe-* To whom correspondence should be addressed. e-mail: hironori.suzuki@phar.toho-u.ac.jp tes, Suglat ® (Ipragliflozin/L-proline cocrystal) and Steglatro ® (Ertugliflozin/L-polyglutamic acid cocrystal), and the neprilysin inhibitor for cardiac insufficiency, Entresto ® (Sacubitril/ Valsartan cocrystal).…”